Background:
Rivastigmine, a reversible AChEI for symptomatic treatment of mild to moderately severe Alzheimer’s dementia is administered in once daily transdermal patches enabling an easier and continuous drug delivery. A novel multi-day (twice week) patch formulation with greater convenience for patients’ therapeutic management, was developed.
Objective:
To assess the bioequivalence under SS conditions of the multiple-day rivastigmine transdermal patch (Test Product, RID-TDS) in comparison to the once daily Exelon® transdermal patch (Reference Product), both at a release rate of 9.5 mg/24 h.
Design:
Single center, open-label, randomized, multiple dose study in healthy male adults in a 2-period, 2-sequence-crossover design with multiple applications.
Methods:
Patches were applied on 11 consecutive days for Exelon® and 4-3-4-day regimen for the multiday test patch (RID-TDS), separated by a 14-day wash-out period. The safety, local tolerability and inhibitory effect of rivastigmine on plasma BuChE activity were also evaluated.
Results:
57 subjects completed the study according to the protocol. Calculated point estimates and 90% CI for all primary parameters (AUC96-264, Cmax96-264 and Cmin96-264) were within the predefined acceptance interval of 80.00 – 125.00%. They were 113.64% (107.33 – 120.33), 105.14% (98.38 – 112.38) and 107.82% (97.78 – 118.89) respectively. Satisfactory adhesion (CI of mean adhesion above 90%) was demonstrated for RID-TDS but not for Exelon®.
Conclusion:
Bioequivalence was demonstrated between RID-TDS mg twice a week and Exelon® once a day in SS. Patch adhesion favored RID-TDS despite the longer dosing interval. Both products were well tolerated.
Trial Registration number:
Protocols are registered in ClinicalTrials.gov: NCT03659435 and EudraCT: 2018-001570-18
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